Post hoc analysis of the CANTREAT randomised trial
Reviewed by Sofia Rokerya

CANTREAT, a Canadian multicentre two-year randomised trial compares treat and extend treatment (T&E) relative to the monthly administration of Ranibizumab in nAMD. Two-hundred and eighty-five treatment-naïve patients with nAMD were randomised to receive either a once-monthly dosing or T&E regimen of ranibizumab across 27 treatment centres in Canada and were followed up for 24 months. This study is the post-hoc analysis of CANTREAT. It explores the relationship between the maximal extension interval tolerated by patients receiving T&E ranibizumab and visual acuity outcomes. Patients in the T&E cohort were subdivided into the following groups based on maximum extension interval: four weeks, six weeks, eight weeks, 10 weeks and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). Patients in the T&E cohort had a mean age of 78.9 ± 7.7 years, were 60.6% female, and were predominantly white. The mean baseline BCVA was 62.1 ± 14.7, 56.3 ± 15.1, 59.3 ± 15.4, 59.1 ± 13.4, and 58.3 ± 13.4 ETDRS letters in the cohorts extended for four, six, eight, 10, and 12 weeks, respectively. At month 24, the change in BCVA from baseline was +8.5 ± 9.3, +7.7 ± 13.8, +4.4 ± 9.6, +4.4 ± 18.5, and +7.8 ± 14.8 letters in the four-, six-, eight-, 10-, and 12-week cohorts, respectively. At month 24, the change in BCVA from baseline was highest in the cohort with a maximum extension interval of four weeks (+8.5 ± 9.3 ETDRS letters), followed by the cohort extended for 12 weeks (+7.8 ± 14.8 letters) and the cohort extended for six weeks (+7.7 ± 13.8 letters). The worst visual acuity gains were in the cohort extended eight weeks (+4.4 ± 9.6 letters) and 10 weeks (+4.4 ± 18.5 letters). The mean baseline CRT was 404.6 ± 133.2, 409.0 ± 114.1, 341.0 ± 99.9, 368.6 ± 116.4, and 382.8 ± 107.5 μm in the cohorts extended for four, six, eight, 10, and 12 weeks, respectively. The CRT at month 24 was 308.0 ± 79.6, 259.6 ± 68.6, 246.8 ± 43.0, 259.4 ± 56.0, and 251.2 ± 57.1 μm in the four-, six-, eight-, 10-, and 12-week cohorts, respectively The change in CRT from baseline was highest in the cohort with a maximum extension interval of six weeks (−143.9 ± 128.9 μm), followed by the cohort extended for 12 weeks (−133.2 ± 108.8 μm) and the cohort extended for 10 weeks (−120.9 ± 105.3 μm). The worst change in CRT from baseline was in the cohort extended four weeks (−79.2 ± 95.0 μm) and eight weeks (−97.7 ± 101.1 μm}. The study concluded that association to extend does not necessarily associate with improved visual acuity outcomes. As seen at month 24, there was a substantially worse change in BCVA between the cohort with a maximum extension interval of 8-10 weeks relative to either the group with a maximum extension interval of four to six weeks or 12 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for four weeks. Future studies are required to establish the predictive factors for successful extension in patients undergoing T&E in nAMD. Strengths: Multicentred, prospective trial with standardised data collection. Limitations: Trial was open label, it was not powered to evaluate the differences in visual acuity outcomes of extension cohort less than six weeks and did not allow for the presence of any intraretinal or subretinal fluid when determining whether to extend further.

Maximal extension interval and visual outcomes in a treat-and-extend protocol: a post hoc analysis of the CANTREAT randomized trial.
Popovica MM, Sheidow T, Baker J, Kertes PJ.
OPHTHALMOLOGICA
2023;(246):123-30.